Neoadjuvant immunotherapy for advanced, resectable non–small cell lung cancer: A systematic review and meta‐analysis

Author:

Wu Yajing1,Verma Vivek2ORCID,Gay Carl M.3,Chen Yujia1,Liang Fei4ORCID,Lin Qiang5,Wang Jianing1,Zhang Wei1,Hui Zhouguang6ORCID,Zhao Min7,Wang Jun1,Chang Joe Y.2ORCID

Affiliation:

1. Department of Radiation Oncology The Fourth Hospital of Hebei Medical University Hebei Clinical Research Center for Radiation Oncology Shijiazhuang China

2. Department of Radiation Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA

3. Department of Head/Neck and Thoracic Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA

4. Department of Biostatistics Zhongshan Hospital Fudan University Shanghai China

5. Department of Oncology North China Petroleum Bureau General Hospital Hebei Medical University Renqiu China

6. Department of VIP Medical Services & Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical Beijing China

7. Department of Oncology Hebei Chest Hospital Shijiazhuang China

Abstract

AbstractBackgroundNeoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non‐small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD‐guided systematic review and meta‐analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes.MethodsEligibility was resectable stage I–III NSCLC and the receipt of programmed death‐1/programmed cell death ligand‐1 (PD‐L1)/cytotoxic T‐lymphocyte–associated antigen‐4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel–Haenszel fixed‐effect or random‐effect model was used, depending on the heterogeneity (I2).ResultsSixty‐six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade ≥3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49–12.97; p < .001), progression‐free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38–0.67; p < .001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36–0.74; p = .0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67–1.52; p = .97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15–0.43; p < .001) and OS (HR, 0.26; 95% CI, 0.10–0.67; p = .005). PD‐L1 expressors (≥1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22–7.03; p = .02).ConclusionsIn patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD‐L1, without increasing toxicities.Plain Language Summary This meta‐analysis of 66 studies showed that neoadjuvant immunotherapy for advanced resectable non‐small cell lung cancer is safe and efficacious. Compared with chemotherapy alone, chemoimmunotherapy improved pathologic response rates and survival, particularly for patients who had tumors that expressed programmed cell death ligand‐1, without increasing toxicities.

Publisher

Wiley

Subject

Cancer Research,Oncology

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